Search Results (2)

Background: CACNA1C gene encodes the alpha 1 subunit of the CaV1.2 L-type Ca2+ channel. Pathogenic variants in this gene have been associated with cardiac rhythm disorders such as long QT syndrome, Brugada syndrome and Timothy syndrome. Recent evidence has suggested the possible association between CACNA1C mutations and neurologically-isolated (in absence of cardiac involvement) phenotypes in children, giving birth to a wider spectrum of CACNA1C-related clinical presentations. However, to date, little is known about the variety of both neurological and non-neurological signs/symptoms in the neurologically-predominant phenotypes. Methods and Results: We conducted a systematic review of neurologically-predominant presentations without cardiac conduction defects, associated with CACNA1C mutations. We also reported a novel de novo missense pathogenic variant in the CACNA1C gene of a children patient presenting with constructional, dressing and oro-buccal apraxia associated with behavioral abnormalities, mild intellectual disability, dental anomalies, gingival hyperplasia and mild musculoskeletal defects, without cardiac conduction defects. Conclusions: The present study highlights the importance of considering the investigation of the CACNA1C gene in children’s neurological isolated syndromes, and expands the phenotype of the CACNA1C related conditions. In addition, the present study highlights that, even in absence of cardiac conduction defects, nuanced clinical manifestations of the Timothy syndrome (e.g., dental and gingival defects) could be found. These findings suggest the high variable expressivity of the CACNA1C gene and remark that the absence of cardiac involvement should not mislead the diagnosis of a CACNA1C related disorder. Full article

Background: Several treatment options have been proposed for pediatric acute-onset neuropsychiatric syndrome/pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection (PANS/PANDAS). Still, no clear therapeutic protocol has been recognized to prevent these neuropsychiatric diseases. The study aims to report on the literature evidence and different treatment strategies related to these disorders. Methods: We analyzed the last 20 years’ English language literature and performed a comprehensive review of the PANS/PANDAS treatment, including studies reporting OCD outcomes post-treatment follow-up. Results: We covered 11 articles in our systematic literature review for a total of 473 patients, of which four studies included 129 surgical subjects and seven papers with 326 medically treated patients. Pooled outcomes analysis, surgical and medical treatment reported an OCD reduction, but no statistical significance was obtained (p < 0.05 for both). Conclusions: Surgical therapy in selected patients can lead to promising results, although further evidence is needed. On the other hand, the role of medical therapy remains controversial, often due to the lack of univocal curative protocols and variable responses depending on the drug used and the timing of administration. Therefore, further investigations are necessary to clarify the most appropriate therapeutic procedure. Full article